Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds

FEBS Lett. 2005 May 9;579(12):2541-5. doi: 10.1016/j.febslet.2005.03.090. Epub 2005 Apr 14.


Females live longer than males in many mammalian species, including humans. Mitochondria from females produce approximately half the amount of H(2)O(2) than males. We have found that females behave as double transgenics overexpressing both superoxide dismutase and glutathione peroxidase. This is due to oestrogens that act by binding to the estrogen receptors and subsequently activating the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NF-kappaB) signalling pathways. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of upregulating antioxidant genes, by hormonal and dietary manipulations, in order to increase longevity is discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Enzyme Activation
  • Estrogens / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Glutathione Peroxidase / metabolism
  • Humans
  • Longevity / drug effects*
  • Male
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Models, Biological
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Phytoestrogens / pharmacology*
  • Sex Factors
  • Species Specificity
  • Superoxide Dismutase / metabolism
  • Up-Regulation*


  • Antioxidants
  • Estrogens
  • NF-kappa B
  • Phytoestrogens
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Mitogen-Activated Protein Kinase Kinases